The dynamin-related GTPase Opa1 is required for glucose-stimulated ATP production in pancreatic beta cells

Zhongyan Zhang, Nobunao Wakabayashi, Junko Wakabayashi, Yasushi Tamura, Woo Jin Song, Sam Sereda, Pascaline Clerc, Brian M. Polster, Susan M. Aja, Mikhail V. Pletnikov, Thomas W. Kensler, Orian S. Shirihai, Miho Iijima, Mehboob A. Hussain, Hiromi Sesaki

Research output: Contribution to journalArticle

Abstract

Previous studies using in vitro cell culture systems have shown the role of the dynamin-related GTPase Opa1 in apoptosis prevention and mitochondrial DNA (mtDNA) maintenance. However, it remains to be tested whether these functions of Opa1 are physiologically important in vivo in mammals. Here, using the Cre-loxP system, we deleted mouse Opa1 in pancreatic beta cells, in which glucose-stimulated ATP production in mitochondria plays a key role in insulin secretion. Beta cells lacking Opa1 maintained normal copy numbers of mtDNA; however, the amount and activity of electron transport chain complex IV were significantly decreased, leading to impaired glucose-stimulated ATP production and insulin secretion. In addition, in Opa1-null beta cells, cell proliferation was impaired, whereas apoptosis was not promoted. Consequently, mice lacking Opa1 in beta cells develop hyperglycemia. The data suggest that the function of Opa1 in the maintenance of the electron transport chain is physiologically relevant in beta cells.

Original languageEnglish (US)
Pages (from-to)2235-2245
Number of pages11
JournalMolecular biology of the cell
Volume22
Issue number13
DOIs
StatePublished - Jul 1 2011

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ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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